The primary aims of the proposed research are two-fold: (a) determination of the three-dimensional structures of tRNA molecules with differing amino acid specificities and biological origin, (b) elucidation of the mode of binding of metals, drugs, dye molecules and complementary oligonucleotides with tRNA. The primary tool will be single crystal x- ray diffraction technique. Work on two different tRNAs viz., phe tRNA (monoclinic) from yeast and arg tRNA (trigonal) from E. coli has been in progress for the past two years. Three approaches are being pursued to obtain structural information: (a) conventional isomorphous replacement method, (b) Patterson search method assuming the presence of helical parts in the molecule, and (c) direct method. Following an extensive survey of heavy atom derivatives of phe tRNA, two satisfactory derivatives have been produced, and are currently being used in the analysis. The Patterson search studies have given the probable positions and orientations of two helical fragments which are approximately at right angles to each other. Work now in progress will use the known helical fragments as the phasing model in an attempt to locate the remaining parts of the molecule. Although the work on arg tRNA has not progressed as far as on phe tRNA, we have found two heavy atom derivatives and data collection is in progress. We also propose to use the Patterson search and rotation function methods to solve the structure of arg tRNA when the coordinates of phe tRNA become available. The long term goals of this work are to determine the structures of a number of other tRNAs, particularly those tRNAs with long variable arms containing base paired secondary structure, aminoacyl synthetases, their complexes with tRNAs and ribosomal RNAs. These structural studies will provide an understanding at the molecular level of the functions and interactions of tRNAs in protein biosynthesis.